A new flavonoid from the leaves of Garcinia mckeaniana Craib and α-glucosidase and acetylcholinesterase inhibitory activities.

From the ethyl acetate extract (EtOAc) of the Vietnamese Garcinia mckeaniana leaves, a new flavone 8-C-glycoside 2'',6''-di-O-acetylvitexin (1), together with six known analogs 2-7 were isolated. Their structures were determined by spectral methods and compared with literature data. In α-glucosidase inhibitory assay, the EtOAc extract and its flavone and biflavone derivatives possessed the significant IC50 range of 9.17-97.53 µM, as compared with that of the positive control acarbose (249 µM). Flavones and biflavones showed are better than flavone glycosides in both α-glucosidase and acetylcholinesterase inhibitory activities[Formula: see text].

Prenylated flavonoids and other constituents from Macaranga indica.

Four new prenylated flavonoids, macarindicins I-IV (1-4) together with ten known compounds, broussoflavonol F (5), vedelianin (6), schweinfurthin E (7), vitexin (8), 2″-rhamnosyl vitexin (9), isovitexin (10), (6R,7E,9R)-9-hydroxy-megastigman-4,7-dien-3-one-9-O-ß-D-glucopyranoside (11), 6S,9R)-roseoside (12), (6S,9S)-roseoside (13), and bridelionoside B (14) were isolated from the leaves of Macaranga indica. Their structures were determined on the basis of extensive spectroscopic methods, including 1D-, 2D-NMR, and MS data. All the isolated compounds were evaluated for their cytotoxic activities against four human cancer cell lines including KB, MCF-7, HepG-2, and LU. As a result, compound 6 significantly exhibited cytotoxic activity against all tested human cancer cell lines with IC50 values ranging from 4.7 to 11.0 µM. Compounds 2, 5, and 7 showed moderate cytotoxic activity with IC50 values ranging from 7.0 to 38.7 µM.

Cytotoxic phenolic compounds isolated from the fruits of Macaranga denticulata.

A new modified geranylated flavonoid, 3'-dehydroxy-solophenol C (1), along with 17 known compounds (2-18) were isolated from the fruits of Macaranga denticulata. Their structures were established by spectral analysis, such as mass spectrometry, 1D-NMR and 2D-NMR. The new geranylated flavonoid 1 showed a moderate cytotoxic activity against the A549 cell line with IC50 value of 16.0 µM. Compound 9 showed the highest cytotoxic activities against KB, HepG2, Lu-1 and MCF7 cell lines with IC50 values of 0.6, 0.8, 1.3 and 1.2 µM, respectively.

New flavonoid and stilbene derivatives from the fruits of Macaranga balansae.

Two new prenylated flavonoids, 4´-methyl-8-prenyltaxifolin (1) and 6,8-diprenyl-4´-methyl-naringenin (2) and a new geranylated stilbene, 4'-deprenyl-4-methoxymappain (3) together with eight known flavonoids (4-11) were isolated from the fruits of Macaranga balansae Gagnep. Their chemical structures were determined by means of spectroscopic methods including 1D, 2D NMR, and MS data. Compound 2 showed the highest cytotoxic activity against PanC1, A549, KB and LU-1 cell lines with IC50 values range from 7.89 to 22.81 µM.

Antimicrobial Lavandulylated Flavonoids from a Sponge-Derived Streptomyces sp. G248 in East Vietnam Sea.

Three new lavandulylated flavonoids, (2S,2''S)-6-lavandulyl-7,4'-dimethoxy-5,2'-dihydroxylflavanone (1), (2S,2''S)-6-lavandulyl-5,7,2',4'-tetrahydroxylflavanone (2), and (2''S)-5'-lavandulyl-2'-methoxy-2,4,4',6'-tetrahydroxylchalcone (3), along with seven known compounds 4-10 were isolated from culture broth of Streptomyces sp. G248. Their structures were established by spectroscopic data analysis, including 1D and 2D nuclear magnetic resonance (NMR), and high-resolution electrospray ionization mass spectrometry (HR-ESI-MS). The absolute configurations of 1-3 were resolved by comparison of their experimental and calculated electronic circular dichroism spectra. Compounds 1-3 exhibited remarkable antimicrobial activity. Whereas, two known compounds 4 and 5 exhibited inhibitory activity against Mycobacterium tuberculosis H37Rv with minimum inhibitory concentration (MIC) values of 6.0 µg/mL and 11.1 µg/mL, respectively.

New dianthramide and cinnamic ester glucosides from the roots of Aconitum carmichaelii.

Four new compounds N-salicyl-3-hydroxyanthranilic acid methyl ester (1), N-(2'-dehydroxysalicyl)-3-hydroxyanthranilic acid methyl ester (2), methyl-4-ß-D-allopyranosyl-ferulate (3), and methyl-4-ß-D-gulopyranosyl-cinnamate (4), along with six known compounds (5-10), were isolated from the roots of Aconitum carmichelii Debx. Their structures were elucidated on the basis of spectral data analysis, including 1D, 2D-NMR, and HR-ESI-MS. Compounds 1 and 2 showed the inhibition of nitric oxide (NO) production with IC50 values of 9.13 and 19.94 µM, respectively.

Antimicrobial metabolites from a marine-derived Actinomycete Streptomyces sp. G278.

Analysis of an antimicrobial extract prepared from culture broth of the marine-derived actinomycete Streptomyces sp. G278 led to the isolation of ten compounds, 1-10. Two compounds, 2,5-Bis(5-tert-butyl-2-benzoxazolyl)thiophene (1), and 3-hydroxyl-2-methylpyridine (2) were isolated from a natural source for the first time. The structures of the isolated compounds were established by their spectral data analysis, including mass spectrometry, 1D-NMR, 2D-NMR, and X-ray crystallographic analysis in case of compound 3. All isolated compounds were evaluated for their antimicrobial activity against a panel of clinically significant microorganisms. Compounds 1 and 3 selectively inhibited Enterococcus faecalis (MIC: 256 µg/mL). Compound 2 was found to have antibacterial and antifungal activity against Escherichia coli (MIC: 64 µg/mL), Salmonella enterica (MIC: 256 µg/mL), Staphylococcus aureus (MIC: 256 µg/mL), Enterococcus faecalis (MIC: 256 µg/mL), and Candida albicans (MIC: 64 µg/mL). Except for compounds 9 and 10, the other known metabolites (4-8) also exhibited antimicrobial activity.

Two new linear acetogenins from the fruits of Goniothalamus gracilipes.

Two new linear acetogenins, gracilipin A (1) and methylsaccopetrin A (2) along with seven known compounds, saccopetrin A (3), 7,3',4'-trimethylquercetin (4), rhamnazin (5), casticin (6), isokanugin (7), melisimplexin (8) and 5-hydroxy-3,7-dimethoxy-3',4'-methylenedioxyflavone (9) were isolated from the fruits of Goniothalamus gracilipes Bân. Their structures were established by spectral analysis, such as mass spectrometry, 1D-NMR, 2D-NMR and circular dichroism (CD). Compounds 1 and 3 showed cytotoxic activity against KB cell line with IC50 values of 14.6 and 15.3 µM, respectively.

Two new sesquiterpenes from the fruits of Fissistigma villosissimum.

Two new sesquiterpenes, namely fissistinone (1) and fissistinol (2), along with ten known compounds (3-12), were isolated from the fruits of Fissistigma villosissimum. Their structures were elucidated on the basis of spectral data analysis, including one-dimensional (1D), two-dimensional (2D)-nuclear magnetic resonance (NMR), and high-resolution-electrospray ionization-mass spectrometry (HR-ESI-MS). Compounds 1-8 were evaluated for their cytotoxic activities against KB cell line; however, all these compounds did not show cytotoxic activity.

Secondary Metabolites from an Actinomycete from Vietnam's East Sea.

Analysis of an antimicrobial extract prepared from culture broth of the marine-derived actinomycete Nocardiopsis sp. (strain G057) led to the isolation of twelve compounds, 1-12. Compound 1 (2-[(2R-hydroxypropanoyl)amino]benzamide) was found to be a new enantiomeric isomer while compounds 2 (3-acetyl-4-hydroxycinnoline) and 3 (3,3'-bis-indole) were isolated from a natural source for the first time. The structures of 1-12 were determined by analyses of MS and 2D NMR data. All compounds were evaluated for their antimicrobial activity against a panel of clinically significant microorganisms. Compound 1 selectively inhibited Escherichia coli (MIC: 16 µg/mL). Compounds 2 and 3 exhibited antimicrobial activity against several strains of both Gram-positive and Gram-negative bacteria, and the yeast Candida albicans. Cytotoxic evaluation of compounds 1-3 against four cancer cell lines (KB, LU-1, HepG-2 and MCF-7) indicated that compound 3 produced a weak inhibition against KB and LU cell lines. Two remaining compounds, 1 and 2 were not cytotoxic, even at the concentration of 128 µg/mL.

Synthesis and biological evaluation of oseltamivir analogues from shikimic acid.

New oseltamivir analogues were designed and synthesized, starting from shikimic acid. Biological evaluation against three human cancer cell lines (KB, MCF7 and Lu-1) showed that many of them exhibited cytotoxic activity. Azides 5 are more active than the corresponding amines 6. Thus, the reduction of the azide group into amine led to the loss of cytotoxicity. The compounds with a cyclohexanemethyloxy group at C-3 were more active than the other investigated compounds belonging to the same series. This cyclohexanemethyloxy group seems to be critical for the cytotoxic activity of this class of compounds. The synthetic oseltamivir analogues 6a-e had no inhibition activity, even at the concentration of 50 microM when they were evaluated for their in vitro influenza A neuraminidase inhibitory activity by an enzymatic assay.

Styryllactones and acetogenins from the fruits of Goniothalamus macrocalyx.

Two new styryllactones, macrocalactone (1) and 3-deoxycardiobutanolide (2), were isolated from the fruits of Goniothalamus macrocalyx Ban (Annonaceae), together with seven known compounds including four acetogenins, annonacin (3), solamin (4), isoannonacin (5), trans-murisolinone (6), and three other compounds, 7-acetylaltholactone (7), beta-caryophyllene-8R,9R-oxide (8) and 2-(2'-hydroxytetracosanoylamino)-octadecane-1,3,4-triol (9). Their structures were determined by spectroscopic and MS analysis. The absolute configuration of 1 was determined by X-ray crystallographic analysis. The structures of the acetogenins were confirmed by liquid chromatography coupled to a hybrid quadrupole-time of flight mass spectrometer, using post-column lithium infusion. The results were compared with the fragmentation obtained with a hybrid linear trap-orbitrap mass spectrometer. Compound 7 had cytotoxicity against KB, HepG2, Lu, and MCF7 cell lines with IC50 values of 13.1, 23.7, 26.3 and 60.2 microM, respectively, whereas annonacin (3) was selectively active against KB cells (IC50 value of 6.5 microM). The discovery of 3-deoxycardiobutanolide (2) from the fruits of this plant revealed that G. macrocalyx could be a valuable natural resource to obtain this compound as it has been previously reported to have a significant cytotoxicity against different cancer cell lines, especially HL-60 cells.

Synthesis and biological evaluation of febrifugine analogues.

A series of febrifugine analogues were designed and synthesized. Antimalarial activity evaluation of the synthetic compounds indicated that these derivatives had a strong inhibition against both chloroquine-sensitive and -resistant Plasmodium falciparum parasites. Many of them were found to be more active than febrifugine hydrochloride. The tested analogues had also a significant cytotoxicity against four cancer cell lines (KB, MCF7, LU1 and HepG2). Among the synthetic analogues, two compounds 17b and 17h displayed a moderate cytotoxicity while they exhibited a remarkable antimalarial activity.

Cytotoxic lignans from fruits of Cleistanthus indochinensis: synthesis of cleistantoxin derivatives.

Two new aryl-tetralin lignans, 1 and 2, were isolated from the fruits of Cleistanthus indochinensis by bioassay-guided purification. Their structures were determined by spectroscopic analysis including MS and 2D NMR. The absolute configurations of 1 and 2 were established from examination of their CD spectra. Compound 1 was cytotoxic against KB cells with an IC(50) value of 0.022 µM, while compound 2 had weaker cytotoxicity, with an IC(50) value of 1.4 µM. When tested against other cancer cell lines (MCF-7, MCF-7R, and HT29), 1 showed an IC(50) of 0.014 against MCF-7R cells and an IC(50) of 0.036 µM against MCF-7 cells. A series of amide derivatives of a new lactone, homoderivatives of 1, were prepared. Of these derivatives, only compound 3 had weak cytotoxicity against KB cells.

Lignans and other constituents from the roots of the Vietnamese medicinal plant Pseuderanthemum palatiferum.

Two new lignans, palatiferin A (1) and palatiferin B (2), were isolated from the roots of Pseuderanthemum palatiferum, together with five known triterpenes, epifriedelanol (3), lupeol (4), lupenone (5), betulin (6), pomolic acid (7), and a dipeptide asperglaucide (8). Their structures were established from 2D NMR and mass spectroscopy. The absolute configuration of 1 and 2 was proposed based on the comparison of their optical rotation activities with those of compounds with similar structures such as wodeshiol and paulownin. The new lignans, palatiferin A (1) and palatiferin B (2) exhibited a moderate cytotoxicity against KB and HepG2 cell lines. However, betulin and lupeol, two abundant compounds from the roots of P. palatiferum, showed cytotoxic and antimicrobial activities.

Synthesis and cytotoxic activity of fluorinated analogues of Goniothalamus lactones. Impact of fluorine on oxidative processes.

Novel fluorinated analogues of goniothalamin 1 and howiinol A 2 have been prepared from trifluorocrotonate derivatives. Trifluoromethyl goniothalamin (R/S) 4 showed a slightly lower activity than 1, while the trifluoromethyl howiinol A 16 exhibited similar activities on several cell lines in the micromolar range. Unlike (R) goniothalamin and howiinol A, trifluoromethyl parent compounds remained unchanged when submitted to biomimetic oxidative systems.

Cytotoxic prenylated isoflavone and bipterocarpan from Millettia pachyloba.

Two new compounds, an isoflavone (1, 6-methoxybarbigerone) and a bipterocarpan (2, pachylobin) were isolated from the grains of Millettia pachyloba (Leguminosae), together with seven known compounds, 5-methoxybarbigerone (3), calopogoniumisoflavone B (4), durmillone (5), jamaicin (6), ichthynone (7), (-)-pisatin (8) and (-)-rotenone (9). The structures were established from spectroscopic analyses, including mass spectrometry and 2D-NMR. Absolute configuration of 2 was proposed based on that of the known compound (-)-pisatine (8). Compounds 1 and 2 exhibited cytotoxicity against KB cells with IC(50) values of 2.0 and 17.6 µM, respectively.